Role of ACE and ACE-2 in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart

Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff's apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.

Renin-Angiotensin-Aldosterone System Inhibitors in COVID-19: A Review

Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.

Recomendación rápida sobre el uso de antihipertensivos IECA/ARA II en pacientes con riesgo o documentación de COVID-19 / Rapid recommendation on the use of ACEI/ARA antihypertensives in patients at risk or with documented COVID-19

Ciertos hallazgos preclínicos generaron preocupación en la comunidad científica y en la población general sobre el uso de inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas del receptor de la angiotensina II (ARAII), y los posibles desenlaces adversos asociados con relación a la infección por el nuevo Coronavirus (SARS-Cov-2).Por este motivo, nos planteamos como objetivo proveer de recomendaciones dinámicas (living recommendations) para el tratamiento con fármacos IECA o ARA II en pacientes con riesgo o documentación de infección por SARS-CoV-2 (en todo su espectro de gravedad). Se utilizó como metodología la adaptación/adopción de guías de práctica clínica bajo el enfoque GRADE, actualizando la evidencia al 7 de abril de 2020 mediante búsquedas en múltiples bases de datos y consultando a un panel multidisciplinario libre de conflictos de interés. Como resultado de este proceso se arribó a la siguiente afirmación: se recomienda, en contexto de la pandemia de COVID-19, en personas que se encuentran en tratamiento con IECA/ARAII, mantener el tratamiento sin cambios por sobre suspenderlo o reemplazarlo por otros fármacos (Recomendación fuerte a favor - calidad de evidencia baja). (AU)

Certain preclinical findings raised concerns in the scientific community and in the general population about the use ofangiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) and the possible adverse outcomes associated with the infection with the new Coronavirus (SARS-Cov-2). For this reason, our objective is to provide living recommendations for treatment with ACEI or ARA in patients with risk or documentation of SARS-CoV-2 infection (inall its severity spectrum). The adaptation/adoption of clinical practice guidelines under the GRADE approach was used as a methodology, updating the evidence as of April 7, 2020, by searching multiple databases and consulting a multidisciplinary panel free of conflicts of interest. As a result of this process, the following statement was reached: it is recommended, in the context of the COVID-19 pandemic, in people who are undergoing treatment with ACEI/ARA, to maintain the treatment unchanged instead of its suspension or replacement with other drugs (Strong recommendation in favor - low quality ofevidence). (AU)

Postoperative angioedema induced by angiotensin-converting enzyme inhibitor: case report / Angioedema pós-operatório induzido por inibidor da enzima conversora da angiotensina: relato de caso

Abstract Background and objectives: Angioedema is a potentially fatal condition that may occur at any time in the perioperative period. It may result from histamine release, hypersensitivity reaction to drugs, or be triggered by bradykinin, in non-allergic reactions of hereditary or acquired etiology. The aim of this report is to report a case of angioedema in the early postoperative period in a patient on antihypertensive medication involving angiotensin-converting enzyme inhibitors. Case report: A 67-year-old male, Afro-descendant, hypertensive, and taken enalapril maleate underwent orthopedic shoulder surgery under general anesthesia combined with brachial plexus block. The procedure lasted 3 hours uneventfully. After discharge from the post-anesthesia care unit, the patient presented with angioedema and severe airway impairment. Tracheal intubation was attempted but it was impossible due to edema affecting the lips, tongue, and oropharyngeal region Emergency cricothyroidotomy was performed. The onset of angioedema had no causal relationship with the administration of any medication; there were no cutaneous manifestations and also not response to therapy for hypersensitivity reaction to drugs, such as antihistamines, corticoid, and adrenaline. It was considered to be mediated by bradykinin, as the patient had already had two similar episodes and was on regular medication (enalapril). The evolution was satisfactory. Conclusion: Angioedema is a potentially fatal condition when it affects the airway, and should be recognized by anesthesiologists and physicians working in the emergency departments.

Resumo Justificativa e objetivos: O angioedema é uma condição potencialmente fatal que pode surgir em qualquer momento no perioperatório. Pode decorrer da liberação de histamina, em uma reação de hipersensibilidade a drogas ou ser desencadeado pela bradicinina, em reações não alérgicas, de etiologia hereditária ou adquirida. O objetivo desse relato é descrever um caso de angioedema, no pós-operatório imediato, em um paciente em uso de medicação anti-hipertensiva da classe dos inibidores da enzima conversora da angiotensina. Relato de caso: Paciente de 67 anos, masculino, negro, hipertenso e em uso do maleato de enalapril, foi submetido a cirurgia ortopédica de ombro sob anestesia geral associada a bloqueio do plexo braquial. O procedimento durou 3 horas, sem intercorrências. Após a alta da sala de recuperação pós-anestésica, apresentou angioedema com grave comprometimento das vias aéreas. Tentou-se fazer intubação traqueal, mas foi impossível devido ao edema que acometia os lábios, a língua e região orofaringeana. Fez-se a cricotireoidostomia de emergência. O aparecimento do angioedema não apresentou relação causal com a administração de qualquer medicação, não houve manifestações cutâneas e também não respondeu à terapêutica para reação de hipersensibilidade a drogas, como anti-histamínicos, corticoide e adrenalina. Foi considerado como mediado pela bradicinina, pois o paciente já havia apresentado dois episódios semelhantes e estava em uso regular de medicação (enalapril). A evolução foi satisfatória. Conclusão: O angioedema é uma condição potencialmente fatal quando atinge as vias aéreas e deve ser de conhecimento do anestesiologista e dos médicos que trabalham nos setores de emergência.

Fracturas costales simétricas asociadas a tos / Symmetrical rib fractures associated with chronic cough: report of one case

Cough may be associated with complications such as syncope, urinary incontinence, pneumothorax, and less frequently, pulmonary hernia and costal fractures. Chronic cough is a cause of rib fractures and when they occur it is likely to affect more than one rib. We report a 53 year-old obese male in treatment with enalapril 10 mg for hypertension with a dry cough lasting five months. He consulted for bilateral chest pain and a Chest X ray examination showed symmetrical fractures in the seventh left and right ribs. Enalapril was discontinued, cough and pain subsided in two weeks.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure / Influência do Polimorfismo Genético da Enzima Conversora de Angiotensina em Dados Ecocardiográficos de Pacientes com Insuficiência Cardíaca Isquêmica

Abstract Background: Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. Objectives: To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Methods: Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. Results: The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. Conclusions: More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD.

Resumo Fundamentos: Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Objetivos: Avaliar a frequência dos polimorfismos genéticos da ECA em pacientes com IC de etiologia isquêmica de uma população do Rio de Janeiro e sua associação com achados ecocardiográficos. Métodos: Avaliação genética do polimorfismo I/D da ECA associada a análise de dados clínicos, laboratoriais e ecocardiográficos de 99 pacientes. Resultados: Foram encontrados 53 alelos I, 145 alelos D, quanto aos genótipos da ECA: 49,5% DD, 47,48% DI, 3,02% II. O tratamento medicamentoso foi otimizado com 98% usando betabloqueadores e 84,8%, IECA ou bloqueador do receptor de angiotensina. Achados ecocardiográficos: diferença entre os diâmetros diastólicos do ventrículo esquerdo (ΔVED): 2,98±8,94 (DD) vs. 0,68±8,12 (DI) vs. -11,0±7,00 (II), p=0,018; piora evolutiva do diâmetro sistólico do VE (VES): 65,3 % DD vs. 19,0 % DI vs. 0,0 % II, p=0,01; do diâmetro diastólico do VE (VED): 65,3 % DD vs. 46,8 % DI vs. 0,0 % II, p=0,03; e da fração de ejeção do VE (FEVE): 67,3 % DD vs. 40,4 % DI vs. 33,3 % II, p=0,024. Correlação com alelo D: ΔFEVE, ΔVES, ΔVED. Conclusões: Foram identificados mais pacientes com piora evolutiva da FEVE e dos diâmetros cavitários do VE no genótipo DD, seguido do DI, sendo o II o de melhor evolução. O mesmo padrão foi observado na ΔVED.

Angiotensin II type 1 receptor blockers as a first choice in patients with acute myocardial infarction

BACKGROUND/AIMS: Angiotensin II type 1 receptor blockers (ARBs) have not been adequately evaluated in patients without left ventricular (LV) dysfunction or heart failure after acute myocardial infarction (AMI). METHODS: Between November 2005 and January 2008, 6,781 patients who were not receiving angiotensin-converting enzyme inhibitors (ACEIs) or ARBs were selected from the Korean AMI Registry. The primary endpoints were 12-month major adverse cardiac events (MACEs) including death and recurrent AMI. RESULTS: Seventy percent of the patients were Killip class 1 and had a LV ejection fraction > or = 40%. The prescription rate of ARBs was 12.2%. For each patient, a propensity score, indicating the likelihood of using ARBs during hospitalization or at discharge, was calculated using a non-parsimonious multivariable logistic regression model, and was used to match the patients 1:4, yielding 715 ARB users versus 2,860 ACEI users. The effect of ARBs on in-hospital mortality and 12-month MACE occurrence was assessed using matched logistic and Cox regression models. Compared with ACEIs, ARBs significantly reduced in-hospital mortality(1.3% vs. 3.3%; hazard ratio [HR], 0.379; 95% confidence interval [CI], 0.190 to0.756; p = 0.006) and 12-month MACE occurrence (4.6% vs. 6.9%; HR, 0.661; 95% CI, 0.457 to 0.956; p = 0.028). However, the benefit of ARBs on 12-month mortality compared with ACEIs was marginal (4.3% vs. 6.2%; HR, 0.684; 95% CI, 0.467 to 1.002; p = 0.051). CONCLUSIONS: Our results suggest that ARBs are not inferior to, and may actually be better than ACEIs in Korean patients with AMI.

Lesão renal aguda em pacientes em uso de inibidor da enzima conversora de angiotensina para tratar insuficiência cardíaca descompensada / Acute kidney injury in patients using angiotensin-converting enzyme inhibitors to treat decompensated heart failure

JUSTIFICATIVA E OBJETIVO: Esse estudo procurou descrevera incidência de lesão renal aguda (LRA) em pacientes com insuficiência cardíaca (IC) descompensada pós uso de inibidor de enzima conversora de angiotensina (IECA) e o perfil clínico-epidemiológico desses pacientes. MÉTODOS: Trata-se de um estudo de coorte prospectiva. Foram incluídos no estudo pacientes com insuficiência cardíaca classe IV segundo critérios doNew York Heart Association (NYHA) descompensada admitidos nas enfermarias de Clínica Médica do Hospital Santo Antônio no período de 01/03/2011 a 30/10/2012. Foram excluídos pacientescom doença renal crônica estágios III, IV, V e com dados incompletos. A lesão renal aguda foi definida de acordo como critério RIFLE (Risk/Injury/Failure/Loss/End-stage). Os dados foram analisados através do programa estatístico SPSS 14.0.Esse projeto foi aprovado pelo Comitê de Ética e Pesquisa do Hospital Santo Antônio. RESULTADOS: Dos 100 pacientes estudados, a maioria era do sexo masculino, de etnia afrodescendentee apresentavam como etiologia da insuficiência cardíaca amiocardiopatia chagásica crônica. O sexo feminino, a presença de hipertensão arterial prévia, maiores valores médios basais depressão arterial sistólica (PAS) e pressão arterial diastólica (PAD)e maiores valores médios de idade foram associados à ocorrência de lesão renal aguda, bem como valores médios mais elevados de creatinina sérica basal. Doses médias maiores de inibidores de enzima conversora de angiotensina e de furosemida venosadurante a primeira semana de tratamento foram associadas à ocorrência lesão renal aguda. A área sob a curva ROC (Receiver Operating Characteristic) Curve (AuROC) para uso de inibidores da enzima conversora de angiotensina foi de 0,70 com p=0,001...

BACKGROUND AND OBJECTIVE: This study sought to describe the incidence of acute kidney injury (AKI) in patients with decompensated heart failure after angiotensin converting enzyme (ACE) inhibitors and the clinical - epidemiological profile of these patients. METHODS: This is a prospective cohort study. Patients with New York Heart Association (NYHA) class IV were included in the study. They were admitted in thewards of Internal Medicine, Hospital Santo Antonio in theperiod from 01/03/2011 to 30/10/2012. Patients with chronic kidney disease stages III, IV, V, and without complete data were excluded. Acute kidney injury was defined according to the RIFLE (Risk/Injury/Failure/Loss/End-stage) criteria. Data were analyzed using SPSS 14.0 statistical program. This project was approved by the Ethics and Research Comitee of Hospital St. Anthony. RESULTS: Of the 100 patients, the majority were male, of african descente and and had Chagas´ cardiomyopathy as a cause of heart failure. Females, the presence of previous hypertension and higher baseline mean of diastolic or sistolic pressure and higher mean values of age were associated with the occurrence of acute kidney injury, as well as higher values of baseline serum creatinine. Higher doses of angiotensin converting enzyme inhibitors and furosemide were associated with the occurrence of renal injury. The area under the Receiver Operating Characteristic (ROC) Curve (AUROC) for angiotensin converting enzyme inhibitors (ACEI) was 0.70 with p-0.001. CONCLUSION: High doses of angiotensin converting enzyme inhibitors and intravenous furosemide are associated with acute kidney injury especially in the first week of introduction of angiotensin converting enzyme inhibitors...

Tratamento medicamentoso atual / Current drug treatment

A elevada prevalência populacional de doença arterial coronária crônica propiciou a melhora dos métodos preventivos, diagnósticos e terapêuticos. A confirmação de isquemia, com ou sem sintomas, trouxe tratamento inovadores visando à redução de eventos agudos, melhora na qualidade de vida e aumento de sobrevida Estudos recentes comparam os resultados do tratamento clínico com outras intervenções e concluíram que o sucesso da intervenção clínica está embasado na otimização terapêutica. Definida a influência dos fatores de risco e os mecanismos fisiopatológicos da doença, o tratamento medicamentoso constitui a base e a sequência de todas as intervenções na doença arterial coronária crônica.

The high prevalence of patients with chronic coronary artery disease has led to the improvement of preventive, diagnostic and therapeutic methods. Confirmation of ischemia with or without symptoms, brought innovative treatment aimed at reducing acute events, improvement in quality of life and increased survival. Recent studies have compared the results of clinical treatment with other interventions and concluded that the success of clinical intervention is based on therapeutic optimization. Once established the inluence of risk factors and physiopathological mechanisms of the disease, drug treatment constitutes the basis and the sequence of all interventionns in chronic artery disease.

Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidney injury after coronary angiography

BACKGROUND/AIMS: With the increasing incidence of cardiovascular disease, angiocardiography using contrast-enhancing media has become an essential diagnostic and therapeutic tool, despite the risk of contrast-medium-induced acute kidney injury (CIAKI). CIAKI may be exacerbated by renin-angiotensin-system (RAS) blockers, which are also used in a variety of cardiovascular disorders. This study evaluated the effects of RAS blockade on CIAKI after coronary angiography. METHODS: Patients who underwent coronary angiography in our hospital between May 2009 and July 2011 were reviewed. Serum creatinine levels before and after coronary angiography were recorded. CIAKI was diagnosed according to an increase in serum creatinine > 0.5 mg/dL or 25% above baseline. RESULTS: A total of 1,472 subjects were included in this study. Patients taking RAS blockers were older, had a higher baseline creatinine level, lower estimated glomerular filtration rate (eGFR), and had received a greater volume of contrast medium. After propensity score matching, no difference was observed between the RAS (+) and RAS (.) groups. Multiple logistic regression identified RAS blockade, age, severe heart failure, contrast volume used, hemoglobin level, and eGFR as predictors of CIAKI. Multiple logistic regression after propensity matching showed that RAS blockade was associated with CIAKI (odds ratio, 1.552; p = 0.026). CONCLUSIONS: This study showed that the incidence of CIAKI was increased in patients treated with RAS blockers.

Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

O uso de inibidores da enzima conversora de angiotensina e sua relação com eventos no pós-operatório de cirurgia de revascularização miocárdica / The use of inhibitors of angiotensin-converting enzyme and its relation to events in the postoperative period of CABG

FUNDAMENTO: Os inibidores da enzima conversora de angiotensina (IECA) reduzem o risco de óbito, infarto agudo do miocárdio (IAM) e acidente vascular encefálico (AVE) em portadores de doença coronariana. No entanto, não há consenso quanto à sua indicação em pacientes que serão submetidos à cirurgia de revascularização miocárdica (CRM). OBJETIVO: Avaliar a relação entre uso pré-operatório de IECA e eventos clínicos após realização da CRM. MÉTODOS: Estudo de coorte retrospectivo. Foram incluídos dados de 3.139 pacientes consecutivos submetidos à CRM isolada em hospital terciário brasileiro, entre janeiro de 1996 e dezembro de 2009. O seguimento dos pacientes foi realizado até a alta hospitalar ou óbito. Desfechos clínicos no pós-operatório foram analisados entre os usuários e os não-usuários de IECA no pré-operatório. RESULTADOS: Cinquenta e dois por cento (1.635) dos pacientes receberam IECA no pré-operatório. O uso de IECA foi preditor independente da necessidade de suporte inotrópico (RC 1,24, IC 1,01-1,47; P=0,01), de insuficiência renal aguda (IRA, RC 1,23, IC 1,01-1,73; P=0,04) e de evolução para fibrilação atrial (FA, RC 1,32, IC 1,02-1,7; P=0,03) no pós-operatório. A mortalidade entre os pacientes que receberam ou não IECA no pré-operatório foi semelhante (10,3 vs. 9,4%, P=0,436), bem como a incidência de IAM e AVE (15,6 vs. 15,0%, P=0,694 e 3,4 vs. 3,5%, P=0,963, respectivamente). CONCLUSÃO: O uso pré-operatório de IECA foi associado a maior necessidade de suporte inotrópico e maior incidência de IRA e FA no pós-operatório, não estando associado ao aumento das taxas de IAM, AVE ou óbito.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce the chance of death, myocardial infarction (MI) and cerebrovascular accident (CVA) in patients with coronary disease. However there is no consensus as to its indication in patients undergoing coronary artery bypass grafting (CABG). OBJECTIVE: To assess the relationship between preoperative use of ACE inhibitors and clinical outcomes after CABG. METHODS: Retrospective cohort study. We included data from 3,139 consecutive patients undergoing isolated CABG in Brazilian tertiary care hospital between January 1996 and December 2009. Follow-up was until discharge or death. Clinical outcomes after surgery were analyzed between users and nonusers of ACE inhibitors preoperatively. RESULTS: Fifty-two percent (n=1,635) of patients received ACE inhibitors preoperatively. The use of ACE inhibitors was an independent predictor of need for inotropic support (OR 1.24, 95% CI 1.01 to 1.47, P = 0.01), acute renal failure (OR 1.23, 95% CI 1.01 to 1.73, P = 0.04) and progression to atrial fibrillation (OR 1.32, 95% CI 1.02 to 1.7, P = 0.03) postoperatively. The mortality rate among patients receiving or not preoperative ACE inhibitors was similar (10.3% vs. 9.4%, P = 0.436), as well as the incidence of myocardial infarction and stroke (15.6% vs. 15.0%, P = 0.694 and 3.4% vs. 3.5%, P = 0.963, respectively). CONCLUSION: The use of preoperative ACE inhibitors was associated with increased need for inotropic support and higher incidence of acute renal failure and postoperative atrial fibrillation, not associated with increased rates of myocardial infarction, stroke or death.

Bloqueo AV completo, reversible, en relación a hiperkalemia grave por enalapril y espironolactona: caso clínico / Complete atrioventricular block, reversible, related to serious hyperkalemia due to enalapril and spironolactone: case report

La hiperkalemia es una de las principales complicaciones potenciales del uso de drogas del tipo IECA, bloqueadores ARAII y antagonistas del receptor de aldosterona, en relación a su dosis, su eventual uso combinado y la función renal del paciente. A continuación se reporta el caso de un paciente de 71 años de edad, hipertenso y diabético que se encontraba en tratamiento con Enalapril 10 mg c/12 h y Furosemida 40 mg a/ 12 h, que sufre una bloqueo aurículo ventricular de 3º grado, secundario a una hiperkalemia de 8.53 mEq/l.

A case of losartan induced angioedema.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) target the renin-angiotensin system and are used in the management of hypertension. Both classes of drugs have similar side effects. ARBs are considered to be much better tolerated than ACE inhibitors with lesser incidence of side effects. Angioedema is a very rare side effect associated with ACE inhibitors (ACEI) and even rarer so with ARBs. The cause for angioedema in ACE inhibitors is said to be the rise in bradykinin levels. It has been postulated that angiotensin II receptor activates the bradykinin-prostaglandin-nitric oxide cascade, resulting in bradykinin-mediated side effects of ARBs such as angioedema, but the true mechanism remains largely unknown. We present here a rare case of late onset angioedema associated with losartan (an ARB) in a female patient. She had been started on an ARB as a first line treatment for uncomplicated mild to moderate hypertension. She had no prior exposure to ACE inhibitors and did not have any other significant medical history. Though rare angioedema is a serious recognized side effect of ARB therapy and the patients started on them should be warned to look for the early signs so as to take corrective action.

Cilazapril-induced pleural effusion: a case report and review of the literature

We describe an unusual case of lymphocytic pleural effusion associated with the use of cilazapril, a novel angiotensin-converting-enzyme inhibitor [ACEI]. An 80-year-old male was prescribed cilazapril for hypertension. He subsequently presented with right chest pain and dry cough. He was found to have a lymphocytic pleural effusion on thoracentesis. Extensive workup, including open pleural biopsy, failed to reveal the etiology of the effusion. However, soon after the withdrawal of cilazapril, his clinical symptoms improved and the effusion disappeared. ACEI-induced pleural effusion has only been rarely reported. Drug-induced pleural effusion should be considered when formulating the differential diagnosis in a patient receiving ACEI